Rb1延缓人脐静脉内皮细胞早熟性衰老与caveolin-1表达的关系

Rb1 protects human umbilical vein endothelial cells from hydrogen peroxide-induced senescence: involvement of caveolin-1

目的:血管内皮细胞衰老是动脉粥样硬化发生的病理生理机制之一。本研究旨在探讨人参皂苷Rb1延缓人脐静脉内皮细胞(HUVECs)早熟性衰老与窖蛋白1(caveolin-1)表达的关系,为延缓HUVECs衰老提供新的靶点。方法:建立60μmol/L过氧化氢(H_2O_2)诱导的HUVECs早熟性衰老模型,根据细胞形态学的变化、衰老相关β-半乳糖苷酶(SA-β-Gal)染色阳性率和细胞周期评估内皮细胞衰老,采用Western blot和激光共聚焦显微成像的方法检测caveolin-1的变化,观察人参皂苷Rb1对HUVECs衰老的作用及其相关的分子机制。结果:60μmol/L H_2O_2可成功地诱导内皮细胞衰老,早熟性衰老的HUVECs体积变大,SA-β-Gal活性明显增加,细胞发生G_1期阻滞,细胞增殖受抑制,caveolin-1表达增多。与H_2O_2处理组相比,人参皂苷Rb1预处理延缓HUVECs早熟性衰老,SA-β-Gal染色阳性细胞百分比降低,G_0/G_1期细胞比例下降,caveolin-1表达减少。结论:人参皂苷Rb1可通过抑制caveolin-1的表达延缓H_2O_2诱导的HUVECs早熟性衰老。

AIM： Endothelial cell senescence has been proposed to be involved in endothelial dysfunction and atherogenesis. This study aims to investigate the effects of ginsenoside Rb1,a major constituent of ginseng,on hydrogen peroxide（ H_2O_2）-induced endothelial cell senescence,and to explore the expression and production of caveolin-1 in H_2O_2-induced premature senescence. METHODS： The senescence of primary human umbilical vein endothelial cells（ HUVECs） was induced by H_2O_2 as judged by morphology inspection,senescence-associated β-galactosidase（ SA-β-Gal） staining and cell cycle detection. The protein expression of caveolin-1 was determined by Western blot and confocal laser-scanning microscopy. RESULTS： Treatment of the HUVECs with H_2O_2 at 60 μmol/L induced premature senescence,as judged by enlarged,flattened cell morphology,increased SA-β-Gal activity and sustained growth arrest. H_2O_2 effectively increased caveolin-1 level. Pretreatment of the HUVECs with Rb1 was found to reverse endothelial cell senescence,as witnessed by a significant decrease in senescent cell numbers and a decreased percentage of G_0/G_1 phase cells. Furthermore,Rb1 administration reversed the H_2O_2-increased protein level of caveolin-1. CONCLUSION： Ginsenoside Rb1 antagonizes H_2O_2-induced endothelial cell senescence through caveolin-1 modulation.